Diffuse large B cell lymphoma (DLBCL) is the most common form of lymphoma and accounts for nearly 40% of all cases of non Hodgkin lymphoma. The disease exhibits a striking clinical heterogeneity. Less than half of the patients are cured with standard multi-agent chemotherapy. On the other hand, over half the patients experience early progression, relapse and death from the disease, when treated with the same regimen. The chemotherapy regimens used in the disease have changed little for nearly 30 years. Although gene expression profiling has uncovered molecular subgroups that comprise this entity, little is known about mechanisms underlying these changes in gene expression. Thus far, a handful of studies have explored the role of mutations in DLBCL tumors. The advent of exon-capture technologies and high throughput sequencing provide new opportunities for the exome-wide identification of mutations that are most likely to result in altered gene and protein expression. Through in-solution exon-capture, we aim to perform an exome-wide screen for clinically relevant mutations that occur in at least 10% of patients. We strongly believe that this study will reveal new aspects of disease biology and potential therapeutic targets. PUBLIC HEALTH RELEVANCE: Our work will allow a better understanding of the genetic basis of lymphomas and enable the development of better treatments in lymphoma